Phenol-containing hydrogels, such as hyaluronic acid-tyramine (HA-Tyr) hydrogels, are useful in many applications, including drug or protein delivery and tissue regeneration. Such hydrogels can be formed from a phenol-containing polymer, such as a HA-Tyr conjugate, in the presence of horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) as catalysts. In conventional techniques, the gelation rate and the crosslinking density in the hydrogel can be adjusted by changing the concentration of HRP or H2O2 in the precursor solution. Such a change typically affects both the gelation rate and crosslinking density.
Certain types of gelatin-based hydrogels have been used as drug carriers or tissue engineering scaffolds. These hydrogels are either chemically crosslinked by covalent bonding, or physically crosslinked by hydrophobic interaction or hydrogen bonding. Typically, chemically crosslinked known gelatin-based hydrogels are crosslinked with cross-linkers such as glutaraldehyde, carbodiimide, or diphenylphosphoryl azide, which can induce cytotoxicity or reduce bioactivity of the active ingredient encapsulated in the hydrogels. Both cytotoxicity and reduced bioactivity limit the application of such hydrogels. Physical crosslinking can avoid inducing cytotoxicity and reduced bioactivity. However, existing physically crosslinked gelatin hydrogels have reduced in vivo stability due to internal mechanical stress and molecular interaction between the hydrogel and the physiological molecules. It is also difficult to adjust the mechanical properties of the physically crosslinked gelatin-based hydrogel. The mechanical properties of the known chemically crosslinked gelatin-based hydrogels can be changed by varying the concentrations of the reagents and catalysts in the production process. However, such adjustments can also affect the formation rate of the hydrogel and are thus constrained.